22-32931181-G-T

Variant names:

• chr22-32931181-G-T
• rs183588
• NM_003490.4:c.461+209C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003490.4(SYN3):​c.461+209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 476,852 control chromosomes in the GnomAD database, including 230,163 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (72047 hom., cov: 32)
  • Exomes 𝑓: 0.99 (158116 hom.)
• Consequence: SYN3 NM_003490.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 0 publications found

Genes affected

SYN3 (HGNC:11496): (synapsin III) This gene is a member of the synapsin gene family. Synapsins encode neuronal phosphoproteins which associate with the cytoplasmic surface of synaptic vesicles. Family members are characterized by common protein domains, and they are implicated in synaptogenesis and the modulation of neurotransmitter release, suggesting a potential role in several neuropsychiatric diseases. The protein encoded by this gene shares the synapsin family domain model, with domains A, C, and E exhibiting the highest degree of conservation. The protein contains a unique domain J, located between domains C and E. Based on this gene's localization to 22q12.3, a possible schizophrenia susceptibility locus, and the established neurobiological roles of the synapsins, this family member may represent a candidate gene for schizophrenia. The TIMP3 gene is located within an intron of this gene and is transcribed in the opposite direction. Alternative splicing of this gene results in multiple splice variants that encode different isoforms. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYN3	NM_003490.4	c.461+209C>A		intron_variant	Intron 4 of 13	ENST00000358763.7	NP_003481.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYN3	ENST00000358763.7	c.461+209C>A		intron_variant	Intron 4 of 13	5	NM_003490.4	ENSP00000351614.2
SYN3	ENST00000472027.1	n.409C>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147920 AN: 152152 Hom.: 71990 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.988

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.977

GnomAD4 exome AF: 0.987 AC: 320345 AN: 324582 Hom.: 158116 Cov.: 3 AF XY: 0.986 AC XY: 166899 AN XY: 169228

African (AFR) AF: 0.931 AC: 9270 AN: 9958

American (AMR) AF: 0.990 AC: 14933 AN: 15080

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 9742 AN: 9968

East Asian (EAS) AF: 1.00 AC: 23463 AN: 23464

South Asian (SAS) AF: 0.966 AC: 28820 AN: 29836

European-Finnish (FIN) AF: 0.994 AC: 22105 AN: 22232

Middle Eastern (MID) AF: 0.977 AC: 1375 AN: 1408

European-Non Finnish (NFE) AF: 0.991 AC: 191859 AN: 193578

Other (OTH) AF: 0.985 AC: 18778 AN: 19058

GnomAD4 genome AF: 0.972 AC: 148036 AN: 152270 Hom.: 72047 Cov.: 32 AF XY: 0.973 AC XY: 72384 AN XY: 74426

African (AFR) AF: 0.926 AC: 38465 AN: 41532

American (AMR) AF: 0.988 AC: 15103 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3394 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5164 AN: 5166

South Asian (SAS) AF: 0.964 AC: 4651 AN: 4824

European-Finnish (FIN) AF: 0.996 AC: 10578 AN: 10624

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67420 AN: 68044

Other (OTH) AF: 0.975 AC: 2059 AN: 2112

Alfa AF: 0.974 Hom.: 48490

Bravo AF: 0.971

Asia WGS AF: 0.974 AC: 3386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.014
DANN	Benign	0.83
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs183588; hg19: chr22-33327166;